Mouse model of tumors with MHC class I downregulation

Reduction of MHC class I expression is one of the most frequent mechanisms of tumor escape from the host immunity. Mouse oncogenic TC-1 cell line and its clones TC-1/A9 and TC-1/dB2m with reversible and irreversible downregulation of MHC class I molecules, respectively, were analyzed by RNA-seq. While TC-1/A9 cells were derived from a tumor that developed in a mouse preimmunized against a tumor antigen, TC-1/dB2m cells were prepared by the deactivation of the beta-2-microglobulin gene using the CRISPR/Cas9 system. Next, subcutaneous tumors were induced with the three cell lines and analysis of tumor microenvironment by bulk RNA-seq was performed in naive tumors and tumors treated with a combined immunotherapy consisting of DNA immunization by a gene gun and i.p. administration of the ODN1826 adjuvant. From the treated tumors, RNA was isolated 2 and 9 days after immunotherapy completion.